Diagnosis, clinical features and prognosis in myocarditis/myocardial inflammation

Renal denervation for modulation of sympathetic activation

Minimal invasive treatment strategies for mitral regurgitation

Grown Up Congenital Heart Disease (GUCH)

Diagnosis, clinical features and prognosis in myocarditis/myocardial inflammation

The diagnosis of myocarditis is a major challenge. Due to the lack of specific clinical symptoms and signs in these patients, there is no uniform clinical definition of myocarditis. At present, endomyocardial biopsy still represents the gold-standard for confirming or ruling out myocardial inflammation. The research of our group in this field centres around the diagnostic performance of magnetic resonance (MR) imaging in patients with suspected myocarditis by applying different imaging sequences at different MR scanners. Therefore, the diagnostic accuracy of different MR imaging protocols is compared to results of endomyocardial biopsy. The aim is to replace invasive endomyocardial one day by MR imaging. We recently engaged into a study called 'MyoRacer. The purpose of this study is to find the best MR imaging protocol with the best diagnostic performance possible with the latest techniques applied. The protocol of this study can be found under clinicaltrials.gov/ct2/show/NCT02177630?term=philipp+lurz&rank=1 (ClinicalTrials.gov Identifier: NCT02177630).

Sympathetic overactivity contributes to the development and perpetuation in a subset of patients with resistant hypertension3. Its negative effects include sodium and water retention, increased renin release, and alterations of renal blood ?ow3. Afferent and efferent sympathetic nerves which travel in the renal artery walls mediate pathological interactions between the central nervous system and the kidneys. Recently, catheter-based disruption of these renal sympathetic nerve fibers using radiofrequency energy has been introduced as a new treatment against resistant hypertension. Initial non-randomized and randomized, non-blinded trials demonstrated a dramatic reduction in systolic and diastolic BP following renal sympathetic denervation (RSD). In contrast, in the recent sham-controlled Simplicity HTN-3 trial of patients with severe treatment-resistant hypertension, RSD led to no significant improvement in BP as compared to the sham-group. Some believe that the results of this trial with the so far most rigorous design commenced the beginning of the end of renal nerve ablation. Proponents of RSD argue that the negative outcome is a consequence of inefficient denervation procedures and suboptimal selection of patients. One aspect that deserves further consideration is that patients recruited into the Simplicity HTN-3 study might represent a population at the most advanced spectrum of the disease with marked and in many cases longstanding hypertension. One could argue that in such patients RSD might be less effective due to irreversible alterations of the anatomic structures and physiological processes supporting chronic BP elevations. We therefore hypothesized that patients with less severe forms of resistant hypertension might be more susceptible to RSD. Therefore, we engaged into the world-wide second sham-controlled trial on RSD to test the hypothesis that RSD is superior to a sham intervention in patients with only mild resistant arterial hypertension. We recently present out results as a late braking trail at TCT 2014, a summary can be found under www.tctmd.com/show.aspx?id=126422.
The protocol of this study can be found under clinicaltrials.gov/ct2/show/NCT01656096?term=steffen+desch&rank=1 (ClinicalTrials.gov Identifier: NCT01656096).

Other areas of research include RSD in patients with treated coarctation and uncontrolled arterial hypertension as well as the effect of repeated RSD in socalled 'non-responder'.

Minimal invasive treatment strategies for mitral regurgitation

In patients with HF functional mitral regurgitation (MR) is a consequence of left ventricular and annular dilatation. Significant MR is seen in 30-50 % of patients with HF depending on severity of left ventricular function. It has been clearly established that MR is associated with increase in mortality risk in HF patients. One year mortality among elderly patients with LVEF < 40 % ranged from 0 % to 57 % depending on the degree of functional MR. In patients with ischemic cardiomyopathy the degree of MR was correlated to LV size and function and moderate to severe MR was associated with 2.4 fold increased risk of death in the VALIANT trial. In a recent study of patients with heart failure on standard medical therapy 4 year risk of cardiac death was 43 % in patients with moderate functional MR versus 6 % in patients with only mild MR. Hence even moderate MR is a major risk factor for early mortality even in patients on contemporary medical treatment.
Surgical correction of MR improves haemodynamics, left ventricular geometry and symptoms, but effect on outcome is questionable especially in patients with non-ischemic cardiomyopathy or ischemic cardiomyopathy where coronary anatomy is not suitable for revascularization. Consequently, in many heart centers only patients with functional MR who are accepted for CABG are offered surgical intervention to correct MR. In the current European HF guidelines surgical correction of functional MR without concomitant CABG is a class IIb indication ("may be considered in selected patients with severe MR").
Percutaneous mitral valve repair using the edge-to-edge technique is a recently developed therapeutic option which might offer correction of MR without the high perioperative risk known to exist in HF patients undergoing open heart surgery. The MitraClip system uses an Alferi-like approach and is placed by transvenous (femoral) and, in turn, transseptal access to the left atrium. In the recently published EVEREST II trial 107 patients with predominantly organic MR underwent implantation with a MitraClip. Acute procedural success (MR ? 1+) was 74 %. Survival was 96 % and 74 % had improved symptoms at 1 year. Complications were rare and there were no clip embolizations.
Our research in this field centers around the risk of cerebral embolism due to MitraClip-implantation, the functional consequences for global and regional biventricular function following MR reduction and comparison of MitraClip with open heart surgery in patients with HF and sever MR.

Grown Up Congenital Heart Disease (GUCH)

Remarkable progress in surgical management of complex congenital heart conditions means that over 85% are now reaching adulthood. In fact, the prevalence of congenital heart disease in the adult population is currently equal to and will soon outweigh that in the paediatric population. One of the major problems for this expanding population is dysfunction of the right ventricular outflow tract (RVOT). Initial surgical repair for complex conditions or repeated surgery for free pulmonary regurgitation often includes the creation of an artificial right ventricle to main pulmonary artery connection. Over time, these conduits are prone to develop valvular incompetence or obstruction. There is clear evidence that pulmonary stenosis and regurgitation are associated with exercise intolerance, arrhythmias and an increased risk of sudden death. Timely pulmonary valve replacement can halt and may reverse such unfavourable outcomes. However, this means that patients have to undergo multiple open-heart surgeries in order to reduce the hemodynamic burden on the right ventricle.
Decision making in these patients with RVOT dysfunction is based on the aim to perform pulmonary valve replacement as late as possible to minimise the total number of open-heart surgeries required in individual patients, but before functional impairment might is irreversible. Importantly, this point of no return in right ventricular pressure and/or volume overload is still unknown and represents one of the most challenging problem in the field of adult congenital heart disease.
Ideally, quality of life, survival and freedom from ventricular arrhythmia should be the endpoints for any study trying to optimise timing of pulmonary valve replacement in patients with congenital heart disease and RVOT dysfunction. However, such studies would require a very long follow-up in large patient populations and will not help to improve the management of these patients in the short-term. Therefore, an in-depth understanding of physiological consequences of altering RV loading and its implications for surrogate, non-invasive outcome parameters such as bi-ventricular function or exercise capacity is crucial for the assessment of procedural success of pulmonary valve replacement.
In 2000, percutaneous pulmonary valve implantation (PPVI), a new, non-surgical technique of heart valve replacement, developed in the late 1990's by Professor Philipp Bonhoeffer, was described. This technique was based on the concept that a heart valve sewn inside a stent could be reduced in size by crimping it onto a balloon catheter, and then introduced through a peripheral vessel to the desired implantation site in the heart. Inflation of the balloon would deploy the valved stent and anchor it within the old dysfunctional valve. This simple principle has formed the basis for a successful clinical programme, which to date has treated more than 800 patients with dysfunction of the pulmonary valve.
This new minimal invasive technique for the treatment of RVOT dysfunction has the potential to postpone open-heart surgery and thereby reduce the number of total operations in these patients have to undergo during their life. Furthermore, for the first time, PPVI provides a clinical model that can assess the acute physiological implications of improving pathological RV loading conditions on above mentioned measures of procedural success, without the confounding effects of cardio-pulmonary bypass, as seen in surgical pulmonary valve replacement.
The aim of our research in this field is to assess thoroughly the impact of altering RV loading on bi-ventricular performance, on the interaction between the two ventricles, and on patients' exercise capacity. These outcome measures of procedural success have been shown to be well-defined predictors of late death in patients with congenital heart disease and RVOT dysfunction. A better understanding of the impact of restoring acceptable RV loading conditions on these outcome measures has the potential to improve management and timing of intervention in patients with RVOT dysfunction.